Role of transient receptor potential vanilloid subetype 1 in the increase of thermal pain threshold by moxibustion

AbstractObjectiveTo explore the role of transient receptor potential vanilloid subetype 1 (TRPV1) in the increase of the thermal pain threshold by moxibustion.MethodsForty Kunming mice (20 ± 2) g were randomized into control group, capsaicin group, capsazepine group, moxibustion group and moxibustion + capsazepine (MC) group with 8 mice in each, and 16 C57BL/6 wild-type mice (18 ± 2) g were randomized into wild-type (WT) control group and WT moxibustion group with 8 mice in each, and 14 TRPV1 knockout mice (18 ± 2) g were randomized into knockout (KO) control group and KO moxibustion group with 7 in each. Each mouse in the capsaicin group was subcutaneously injected with the amount of 0.1 mL/10 g into L5 and L6 spinal cords; each mouse in the capsazepine group was intraperitoneally injected with the amount of 0.1 mL/10 g. Similarly, each mouse in the moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords. Each mouse in MC group was intraperitoneally injected with the amount of 0.1 mL/10 g first, then after 15 min was given a suspended moxibustion for 20 min on L5 and L6 spinal cords. Each mouse in WT moxibustion group and KO moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords. The control group, WT control group and KO control group were of no treatment in any way. After all treatments were completed, the digital-display measurement instrument for thermal pain was used to measure the threshold of thermal pain in each group respectively.ResultsCompared with the control group, the thresholds of thermal pain in the moxibustion group and MC group were significantly increased (P <0.01); no significant changes in the thresholds in the capsaicin group and the capsazepine group (P > 0.05); compared with moxibustion group, he threshold of thermal in MC group was obviously decreased (P < 0.01). Compared with WT control group, the threshold of thermal pain in WT moxibustion group was significantly increased (P < 0.01); compared with KO control group, no changes in the threshold in KO moxibustion group (P > 0.05).ConclusionTRPV1 participated in the process of increasing the threshold of thermal pain by stimulating L5 and L6 of mice spinal cord with burning mosa-stick

The CCAAT box-binding transcription factor NF-Y regulates basal expression of human proteasome genes

AbstractProtein degradation by the proteasome plays an important role in all major cellular pathways. Aberrant proteasome activity is associated with numerous human diseases including cancer and neurological disorders, but the underlying mechanism is virtually unclear. At least part of the reason for this is due to lack of understanding of the regulation of human proteasome genes. In this study, we found that a large set of human proteasome genes carry the CCAAT box in their promoters. We further demonstrated that the basal expression of these CCAAT box-containing proteasome genes is regulated by the transcription factor NF-Y. Knockdown of NF-YA, an essential subunit of NF-Y, reduced proteasome gene expression and compromised the cellular proteasome activity. In addition, we showed that knockdown of NF-YA sensitized breast cancer cells to the proteasome inhibitor MG132. This study unveils a new role for NF-Y in the regulation of human proteasome genes and suggests that NF-Y may be a potential target for cancer therapy

Tera-sample-per-second arbitrary waveform generation in the synthetic dimension

The synthetic dimension opens new horizons in quantum physics and topological photonics by enabling new dimensions for field and particle manipulations. The most appealing property of the photonic synthetic dimension is its ability to emulate high-dimensional optical behavior in a unitary physical system. Here we show that the photonic synthetic dimension can transform technical problems in photonic systems between dimensionalities, providing unexpected solutions to technical problems that are otherwise challenging. Specifically, we propose and experimentally demonstrate a photonic Galton board (PGB) in the temporal synthetic dimension, in which the temporal high-speed challenge is converted into a spatial fiber-optic length matching problem, leading to the experimental generation of tera-sample-per-second arbitrary waveforms. Limited by the speed of the measurement equipment, waveforms with sampling rates of up to 341.53 GSa/s are recorded. Our proposed PGB operating in the temporal synthetic dimension breaks the speed limit in a physical system, bringing arbitrary waveform generation into the terahertz regime. The concept of dimension conversion offers possible solutions to various physical dimension-related problems, such as super-resolution imaging, high-resolution spectroscopy, time measurement, etc

A Poisson mixture model to identify changes in RNA polymerase II binding quantity using high-throughput sequencing technology

We present a mixture model-based analysis for identifying differences in the distribution of RNA polymerase II (Pol II) in transcribed regions, measured using ChIP-seq (chromatin immunoprecipitation following massively parallel sequencing technology). The statistical model assumes that the number of Pol II-targeted sequences contained within each genomic region follows a Poisson distribution. A Poisson mixture model was then developed to distinguish Pol II binding changes in transcribed region using an empirical approach and an expectation-maximization (EM) algorithm developed for estimation and inference. In order to achieve a global maximum in the M-step, a particle swarm optimization (PSO) was implemented. We applied this model to Pol II binding data generated from hormone-dependent MCF7 breast cancer cells and antiestrogen-resistant MCF7 breast cancer cells before and after treatment with 17β-estradiol (E2). We determined that in the hormone-dependent cells, ~9.9% (2527) genes showed significant changes in Pol II binding after E2 treatment. However, only ~0.7% (172) genes displayed significant Pol II binding changes in E2-treated antiestrogen-resistant cells. These results show that a Poisson mixture model can be used to analyze ChIP-seq data

A C. elegans neuron both promotes and suppresses motor behavior to fine tune motor output [preprint]

How neural circuits drive behavior is a central question in neuroscience. Proper execution of motor behavior requires the precise coordination of many neurons. Within a motor circuit, individual neurons tend to play discrete roles by promoting or suppressing motor output. How exactly neurons function in specific roles to fine tune motor output is not well understood. In C. elegans, the interneuron RIM plays important yet complex roles in locomotion behavior. Here, we show that RIM both promotes and suppresses distinct features of locomotion behavior to fine tune motor output. This dual function is achieved via the excitation and inhibition of the same motor circuit by electrical and chemical neurotransmission, respectively. Additionally, this bi-directional regulation contributes to motor adaptation in animals placed in novel environments. Our findings reveal that individual neurons within a neural circuit may act in opposing ways to regulate circuit dynamics to fine tune behavioral output

Causal relationships between lung cancer and sepsis: a genetic correlation and multivariate mendelian randomization analysis

BackgroundFormer research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear.MethodThis study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness.ResultsLDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, p = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083–1.269, p = 8.29 × 10−5, Pfdr = 2.49 × 10−4), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021–1.181, p = 0.012, Pfdr = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024–1.178, p = 0.009, Pfdr = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047–1.277, p = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship (p &gt; 0.05 and Pfdr &gt; 0.05).ConclusionThe study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients

A C. elegans neuron both promotes and suppresses motor behavior to fine tune motor output

How neural circuits drive behavior is a central question in neuroscience. Proper execution of motor behavior requires precise coordination of many neurons. Within a motor circuit, individual neurons tend to play discrete roles by promoting or suppressing motor output. How exactly neurons function in specific roles to fine tune motor output is not well understood. In C. elegans, the interneuron RIM plays important yet complex roles in locomotion behavior. Here, we show that RIM both promotes and suppresses distinct features of locomotion behavior to fine tune motor output. This dual function is achieved via the excitation and inhibition of the same motor circuit by electrical and chemical neurotransmission, respectively. Additionally, this bi-directional regulation contributes to motor adaptation in animals placed in novel environments. Our findings reveal that individual neurons within a neural circuit may act in opposing ways to regulate circuit dynamics to fine tune behavioral output

Treatment of Unruptured Vertebral Artery Aneurysm Involving Posterior Inferior Cerebellar Artery With Pipeline Embolization Device

Background: Treatment of unruptured vertebral artery aneurysm involving posterior inferior cerebellar artery (PICA) is challenging. The experience of pipeline embolization device (PED) therapy for these lesions is still limited.Objective: To evaluate the safety and efficacy of the PED for unruptured vertebral artery aneurysm involving PICA.Methods: Thirty-two patients with unruptured vertebral artery aneurysm involving PICA underwent treatment with PED were retrospectively identified. Procedure-related complications, PICA patency, clinical, and angiographic outcomes were analyzed.Results: Thirty-two aneurysms were successfully treated without any procedure-related complications. Images were available in 30 patients (93.8%) during a period of 3–26 months follow-up (average 8.4 months), which confirmed complete occlusion in 17 patients (56.5%), near-complete occlusion in 9 patients (30%), and incomplete occlusion in one patient (3.3%). Parent artery occlusion (PAO) was occurred in 3 patients (10%). Twenty-eight of 30 PICA remained patent. The two occlusions of PICA were secondary to PAO. At a mean of 20.7 months (range 7–50 months) clinical follow-up, all the patients achieved a favorable outcome without any new neurological deficit.Conclusion: PED seems to be a safe and effective alternative endovascular option for patients with unruptured vertebral artery aneurysm involving PICA

Ischemic Duration and Frequency Determines AKI-to-CKD Progression Monitored by Dynamic Changes of Tubular Biomarkers in IRI Mice

Ischemia reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI). However, the pathogenesis and biomarkers predicting the progression of IRI-induced AKI to chronic kidney disease (CKD) remain unclear. A side-by-side comparison between different IRI animal models with variable ischemic duration and episodes was performed. The dynamic changes of KIM-1 and NGAL continuously from AKI to CKD phases were studied as well. Short-term duration of ischemia induced mild renal tubule-interstitial injury which was completely reversed at acute phase of kidney injury, while long-term duration of ischemia caused severe tubular damage, cell apoptosis and inflammatory infiltration at early disease stage, leading to permanent chronic kidney fibrosis at the late stage. Repeated attacks of moderate IRI accelerated the progression of AKI to CKD. Different from serum and urine levels of KIM-1 that increased at acute phase of IRI then declined gradually in chronic phase, NGAL increased continuously during AKI-to-CKD transition. Severity and frequency of ischemia injury determines the progression and outcome of ischemia-induced AKI. Inflammation, apoptosis and fibrogenesis likely participate in the progression of AKI to CKD. Both KIM-1 and NGAL enable noninvasive and early detection of AKI, but NGAL is associated better with the process of AKI-to-CKD progression